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Objective. This multicenter study aimed to investigate the role of preoperative lymphatic mapping and sentinel node biopsy (SNB) as well as the impact of negative SNB on loco-regional control and survival in vulvar melanoma patients with clinically negative nodes (cN0).Methods. Patients who had a proven vulvar melanoma with a Breslow thickness of 1-4 mm, cN0 and under-went a preoperative lymphatic mapping followed by SNB between July 2013 and March 2021 were retrospec-tively included. Groin recurrence and mortality rate were calculated as absolute and relative frequency. Disease-free survival (DFS) and overall survival (OS) were assessed by the Kaplan-Meier method. We provided a systematic review, searching among PubMed/Medline and Embase libraries. A total of 6 studies were identified (48 patients).Results. A total of 18 women were included. Preoperative planar images showed 51 SNs in 28 groins. Additional SPECT/CT images were acquired in 5/18 cases; SNs were identified pre-and intra-operatively in all cases. A total of 65 SNs were excised from 28 groins. A total of 13/18 (72.2%) patients (21/28 groins, 75%) had negative SNs with no groin recurrences and 12/13 (92.3%) were still alive at last follow-up. Five out of the 18 (27.8%) patients (7/28 groins, 25%) had positive SNs, 2/5 (40%) patients died of cancer after 26.2 and 33.8 months, respectively. The median DFS and OS for the entire cohort were 17.9 months (95% CI, 10.3-19.9) and 65.0 months (95% CI, 26.2-infinite), respectively. The probability of DFS and OS at 3 years were 15.5% (95% CI, 2.6-38.7) and 64.3% (95% CI, 15.5-90.2), respectively.Conclusions. The use of preoperative lymphatic mapping followed by SNB permits a precise and minimally in-vasive surgical approach in cN0 vulvar melanoma patients. Negative SNB is associated with low risk of groin re-lapse and good survival.(c) 2023 Elsevier Inc. All rights reserved.

Simple Summary Inguinal node status represents one of the key elements in defining prognosis and treatment strategies in vulvar cancer patients. Preoperative lymph node staging is still a challenging topic. Several imaging methods are currently recommended in the guidelines (CT, PET/CT, MRI, US) based on performance data that are still not conclusive in the literature. Recently, ultrasound is emerging as the method of choice for preoperative evaluation of the inguinofemoral LN, but only when performed by experienced operators, given the limited reliability of subjective evaluation by unskilled operators. The morphonode predictive model represents an artificial intelligence tool that aims to overcome this limitation by supporting the standard ultrasound in adequately predicting the presence of lymph node metastases for improving preoperative surgical planning. We plan to proceed with further multicenter prospective validation and further develop the actual model, including both clinical and biological data. Ultrasound examination is an accurate method in the preoperative evaluation of the inguinofemoral lymph nodes when performed by experienced operators. The purpose of the study was to build a robust, multi-modular model based on machine learning to discriminate between metastatic and non-metastatic inguinal lymph nodes in patients with vulvar cancer. One hundred and twenty-seven women were selected at our center from March 2017 to April 2020, and 237 inguinal regions were analyzed (75 were metastatic and 162 were non-metastatic at histology). Ultrasound was performed before surgery by experienced examiners. Ultrasound features were defined according to previous studies and collected prospectively. Fourteen informative features were used to train and test the machine to obtain a diagnostic model (Morphonode Predictive Model). The following data classifiers were integrated: (I) random forest classifiers (RCF), (II) regression binomial model (RBM), (III) decisional tr

Introduction: Surgical treatment is the gold standard of care for vulvar cancer and is burdened by a high risk of wound complications due to the poor healing typical of the female genital area. Moreover, this malignancy has a high risk of local relapse even after wide excision. For these reasons, secondary reconstruction of the vulvoperineal area is a relevant and challenging scenario for gynecologists and plastic surgeons. The presence of tissue already operated on and undermined, scars, incisions, the possibility of previous radiation therapy, contamination of urinary and fecal pathogens in the dehiscent wound or ulcerated tumor, and the unavailability of some flaps employed during the primary procedure are typical complexities of this surgery. Due to the rarity of this tumor, a rational approach to secondary reconstruction has never been proposed in the literature. Methods: In this observational retrospective study, we reviewed the clinical data of patients affected by vulvar cancer who underwent secondary reconstruction of the vulvoperineal area in our hospital between 2013 and 2023. Oncological, reconstructive, demographic, and complication data were recorded. The primary outcome measure was the incidence of wound complications. The secondary outcome measure was the indication of the different flaps, according to the defect, to establish an algorithm for decision-making. Results: Sixty-six patients were included; mean age was 71.3 ± 9.4 years, and the mean BMI was 25.1 ± 4.9. The mean size of the defect repaired by secondary vulvar reconstruction was 178 cm2 ± 163 cm2. Vertical rectus abdominis myocutaneous (VRAM), anterolateral thigh (ALT), fasciocutaneous V-Y (VY), and deep inferior epigastric perforator (DIEP) were the flaps more frequently employed. We observed five cases of wound breakdown, one case of marginal necrosis of an ALT flap, and three cases of wound infection. The algorithm we developed considered the geometry and size of the defect and the flap

Simple Summary Currently, around 30% of vulvar cancer cases at first diagnosis are spread to the inguinal lymph nodes. Preoperative staging of patients affected by vulvar carcinoma is still a hot topic. To date, MRI has shown a great diagnostic accuracy on defining disease extension to soft tissue and deep organs. At present, regarding the study of inguinal nodes, the PET/CT scan has shown a high negative predictive value, although in the presence of a suspicious/positive report it should be taken with caution. We report the results of a study aimed to investigate the role of groin ultrasound in the assessment of lymph nodal status in vulvar cancer. Furthermore, this review represents the most accurate collection of papers available in the literature. This work demonstrates that groin ultrasound can be considered a valuable tool for risk assessment of the presence of groin lymph node metastases. Achieving a high diagnostic accuracy would allow tailored surgical planning with access to minimally invasive surgery techniques for an increasing number of patients. Objective. To determine the efficacy of ultrasound in assessing the inguinal lymph nodes in patients with vulvar cancer. Methods. A systematic review of published research up to October 2020 that compares the results of ultrasound to determine groin node status with histology was conducted. All study types that reported primary data on the role of ultrasound in the evaluation of groin lymph nodes in vulvar cancer were included in the systematic review. Data retrieved from the included studies were pooled in random-effects meta-analyses. Results. After the screening and selection process, eight articles were deemed pertinent for inclusion in the systematic review and meta-analysis. The random-effects model showed a pooled Se of 0.85 (95% CI: 0.81-0.89), Sp of 0.86 (95% CI: 0.81-0.91), PPV of 0.65 (95% CI: 0.54-0.79) and NPV of 0.92 (95% CI: 0.91-0.94). There was a pooled LR+ and LR- of 6.44 (95% CI: 3.72-11.4) a

Simple Summary In this retrospective observational study, we evaluated data from patients with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NACT) in order to better define the impact of germline BRCA1/2 (gBRCA1/2) mutation status on outcomes in this patient population. Our results show that patients with BRCA1/2 mutation had a higher pathologic complete response (pCR) rate than non-mutated patients; nevertheless, the benefit was confirmed only in the subset of patients who received a platinum-based NACT. Furthermore, pCR was associated with improved Event Free Survival (EFS) and Overall Survival (OS), regardless of BRCA1/2 mutation status and type of NACT received. Long-term follow-up analyses are needed to further define the impact of gBRCA mutation status in patients with early-TNBC. Triple-negative breast cancer (TNBC) is characterized by earlier recurrence and shorter survival compared with other types of breast cancer. Moreover, approximately 15 to 25% of all TNBC patients harbor germline BRCA (gBRCA) 1/2 mutations, which confer a more aggressive phenotype. However, TNBC seems to be particularly sensitive to chemotherapy, the so-called 'triple negative paradox'. Therefore, Neoadjuvant chemotherapy (NACT) is currently considered the preferred approach for early-stage TNBC. BRCA status has also been studied as a predictive biomarker of response to platinum compounds. Although several randomized trials investigated the addition of carboplatin to standard NACT in early-stage TNBC, the role of BRCA status remains unclear. In this retrospective analysis, we evaluated data from 136 consecutive patients with Stage I-III TNBC who received standard NACT with or without the addition of carboplatin, in order to define clinical features and outcomes in BRCA 1/2 mutation carriers and non-carrier controls. Between January 2013 and February 2021, 67 (51.3%) out of 136 patients received a standard anthracyclines/taxane regimen and 69 (50.7%) patie

Objective: The goal of this study was to assess the feasibility and safety of a retrograde extraperitoneal trans-inguinal novel approach to pelvic lymphadenectomy in vulvar cancer patients. The secondary objectives were to assess complications (early and late) and oncological outcomes. Methods: In this pilot study, all patients referred to our institution from November 2019 to May 2021 were evaluated. The inclusion criteria were patients diagnosed with primary/recurrent vulvar cancer and who were candidates for concomitant groin and pelvic lymph node dissection. A consecutive sampling was planned during the study period. After conventional inguino-femoral lymph nodal dissection, ipsilateral extraperitoneal trans-inguinal pelvic lymphadenectomy (TRIPLE) was performed through a groin incision. Clinical data, type of treatment, perioperative complications, and follow-up were evaluated. Results: 13 patients (8 primary, 5 recurrent vulvar cancer) underwent 16 TRIPLE procedures (10 unilateral, 3 bilateral). The median age was 69 years (range 58-93 years); 8 patients had comorbidities (61.5%). Up front locoregional radiotherapy was previously performed in two cases (15.4%). The pathology report showed metastatic lymph nodes in 20 (87%) groins and 11 (68.8%) pelvic sites; the mean number of removed and metastatic pelvic lymph nodes was 12.1 (range 5-33) and 2.9 (range 0-18), respectively. No intra-operative site-specific complications occurred. One (5.9%) post-operative site-specific complication was reported (pelvic abscess, grade 2), which was treated with antibiotics. One patient died due to concomitant pneumonia. No unilateral pelvic lymph node recurrence occurred during follow-up (median 13 months, range 2-43 months); 3 patients (23.1%) had distant site recurrence (median disease-free survival 9 months). Conclusions: TRIPLE seems to be a feasible and safe technique, providing adequate lymph node dissection. Despite being a high-risk and fragile population, morbidity wa

Background and Objectives Lower extremity lymphedema (LEL) is one of the most relevant chronic and disabling sequelae after gynecological cancer therapy involving pelvic lymphadenectomy (PL). Supermicrosurgical lymphaticovenular anastomosis (LVA) is a safe and effective procedure to treat LEL, particularly indicated in early-stage cases when conservative therapies are insufficient to control the swelling. Usually, preoperative assessment of these patients shows patent and peristaltic lymphatic vessels that can be mapped throughout the limb to plan the sites of skin incision to perform LVA. The aim of this study is to report the efficacy of our approach based on planning LVA in three areas of the lower limb in improving early-stage gynecological cancer-related lymphedema (GCRL) secondary to PL. Materials and Methods We retrospectively reviewed the data of patients who underwent LVA for the treatment of early-stage GCRL following PL. Patients who had undergone groin dissection were excluded. Our preoperative study based on indocyanine green lymphography (ICG-L) and color doppler ultrasound (CDU) planned three incision sites located in the groin, in the medial surface of the distal third of the thigh, and in the upper half of the leg, to perform LVA. The primary outcome measure was the variation of the mean circumference of the limb after surgery. The changes between preoperative and postoperative limbs’ measures were analyzed by Student’s t-test. p values < 0.05 were considered significant. Results Thirty-three patients were included. In every patient, three incision sites were employed to perform LVA. A total of 119 LVA were established, with an average of 3.6 for each patient. The mean circumference of the operated limb showed a significant reduction after surgery, decreasing from 37 cm 4.1 cm to 36.1 cm 4.4 (p < 0.01). Conclusions Our results suggest that in patients affected by early-stage GCRL secondary to PL, the placement of incision sites in all the anat

Introduction: Surgical therapy for vulvar cancer involves wide defects that often require flap-based reconstruction. The goal of the reconstruction is fast wound healing with low donor site morbidity. Materials and methods: This is a retrospective observational cohort study in which we reviewed all patients who underwent surgery for vulvar cancer followed by reconstruction using the Superficial Circumflex Iliac Artery Perforator (SCIP) flap between 2015 and 2020. The primary outcome measure of this investigation was the incidence of wound complications. The secondary outcomes were the surgical indications in terms of establishing the anatomical subunits involved in the resection that made us choose this flap for reconstruction. This study adheres to the STROBE guidelines. Results: Thirty-two patients were included; in two cases, the flap was performed bilaterally for a total of 34 SCIP flaps. The mean age of patients was 70.6 ± 8.6 years, and the mean BMI was 26.8 ± 4.7. The SCIP flap was always feasible. The mean flap size was 128.8 ± 74.3cm2. Three patients showed wound complications. In every patient, the defect involved the vulva, perineum and inguinal area; in 18 patients, the mons pubis was also involved. The mean follow-up was 30 months. During the follow-up, six patients died, and four showed local or nodal cancer relapse. Conclusion: Our results suggest that the advantages of SCIP flap for the reconstruction of vulvoperineal defects secondary to vulvar cancer surgery include low complication rate, minimal donor site morbidity, quick dissection, proximity of donor and recipient sites, possibility to harvest large skin islands of variable thickness and chimeric flaps.

BACKGROUND: 'Severe acute respiratory syndrome coronavirus-2' (SARS-CoV-2) infection has dramatically affected the management of patients with cancer, who are most vulnerable to the consequences of the infection. Patients with vulvar cancer are frequently elderly and affected by multiple co-morbidities, thus representing a particularly frail population. OBJECTIVE: To assess the clinical impact of the SARS-CoV-2 infection among patients scheduled for treatment for active vulvar cancer. METHODS: Data on patients with vulvar tumors referred to Fondazione Policlinico Universitario Agostino Gemelli IRCCS between February 2020 and July 2021 were retrospectively analyzed. Patients with a positive reverse transcription polymerase chain reaction in nasopharyngeal swab were considered as positive for SARS-Cov-2. RESULTS: One hundred and ninety-one patients with vulvar cancer were evaluated and scheduled for treatment. The median age was 72 years (range 35-94). Seven (3.7%) patients were diagnosed with SARS-Cov-2 infection: three (42.9%) had their treatment delayed, with no apparent consequences, two (28.6%) had their treatment delayed and later abandoned because of clinical worsening due to oncologic disease progression, and two (28.6%) contracted the infection in the post-operative period and died due to respiratory complications. CONCLUSIONS: In most cases the infection had major clinical implications, being associated with significant delays in oncologic treatments and extremely high mortality when contracted in the post-operative period.

Gynecological cancers require complex intervention since patients have specific needs to be addressed. Centralization to high-volume centers improves the oncological outcomes of patients with gynecological cancers. Research in gynecological oncology is increasing thanks to modern technologies, from the comprehensive molecular characterization of tumors and individual pathophenotypes. Ongoing studies are focusing on personalizing therapies by integrating information across genomics, proteomics, and metabolomics with the genetic makeup and immune system of the patient. Hence, several challenges must be faced to provide holistic benefit to the patient. Personalized approaches should also recognize the unmet needs of each patient to successfully deliver the promise of personalized care, in a multidisciplinary effort. This may provide the greatest opportunity to improve patients’ outcomes. Starting from a narrative review on gynecological oncology patients’ needs, this article focuses on the experience of building a research and care infrastructure for personalized patient management.

In centers with access to high-end ultrasound machines and expert sonologists, ultrasound is used to detect metastases in regional lymph nodes from melanoma, breast cancer and vulvar cancer. There is, as yet, no international consensus on ultrasound assessment of lymph nodes in any disease or medical condition. The lack of standardized ultrasound nomenclature to describe lymph nodes makes it difficult to compare results from different ultrasound studies and to find reliable ultrasound features for distinguishing non-infiltrated lymph nodes from lymph nodes infiltrated by cancer or lymphoma cells. The Vulvar International Tumor Analysis (VITA) collaborative group consists of gynecologists, gynecologic oncologists and radiologists with expertise in gynecologic cancer, particularly in the ultrasound staging and treatment of vulvar cancer. The work herein is a consensus opinion on terms, definitions and measurements which may be used to describe inguinal lymph nodes on grayscale and color/power Doppler ultrasound. The proposed nomenclature need not be limited to the description of inguinal lymph nodes as part of vulvar cancer staging; it can be used to describe peripheral lymph nodes in general, as well as non-peripheral (i.e. parietal or visceral) lymph nodes if these can be visualized clearly. The association between the ultrasound features described here and histopathological diagnosis has not yet been established. VITA terms and definitions lay the foundations for prospective studies aiming to identify ultrasound features typical of metastases and other pathology in lymph nodes and studies to elucidate the role of ultrasound in staging of vulvar and other malignancies. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Locally advanced vulvar cancer (LAVC) is a challenging disease, requiring multidisci-plinary management. The aim of this review is to propose an integrated clinical approach including radiotherapy (RT) in the multidisciplinary management of LAVC to customize the treatment. A review of the literature was conducted on PubMed, Scopus, and Cochrane library to acquire all relevant studies on RT in LAVC. Based on the available evidence, RT, with or without concurrent chemotherapy, has a relevant role as adjuvant and exclusive treatment or in the neoadjuvant setting. However, multicentric prospective trials are needed to define the best treatment options based on tumor and patient characteristics. A multidisciplinary and multidimensional assessment can also be useful to identify the most suitable approach, considering patients’ age and comorbidities, in view of a better treatment personalization.

Purpose: This retrospective study aimed to assess the diagnostic performance of preoperative [18F]FDG-PET/CT in predicting the groin and pelvic lymph node (LN) status in a large single-centre series of vulvar cancer patients. Methods: Between January 2013 and October 2018, among all consecutive women with proven vulvar cancer submitted to [18F]FDG-PET/CT, 160 patients were included. LNs were analysed by two qualitative methods assessing PET information (defined as visual assessment) and a combination of PET and low-dose CT information (defined as overall assessment), respectively, as well as semi-quantitative analysis (LN-SUVmax). Sensitivity, specificity, accuracy, positive and negative predictive values (PPV and NPV) in predicting the groin and pelvic LN status were calculated in the overall study population; a subset analysis of groin parameters in clinically/ultrasonography negative patients was also performed. Histopathology was the reference standard. Results: All patients underwent vulvar and inguinofemoral LN surgery, and 35 pelvic LN surgery. Overall, 338 LN sites (296 groins and 42 pelvic sites) were histologically examined with 30.4% prevalence of metastatic groins and 28.6% for metastatic pelvic sites. In the overall study population, sensitivity (95% confidence interval, CI), specificity (95% CI), accuracy (95% CI), PPV (95% CI) and NPV (95% CI) at the groin level were 85.6% (78.3–92.8), 65.5% (59.0–72.0), 71.6% (66.5–76.8), 52.0% (44.0–60.1) and 91.2% (86.7–95.8) for visual assessment; 78.9% (70.5–87.3), 78.2% (72.5–83.8), 78.4% (73.7–83.1), 61.2% (52.3–70.1) and 89.4% (85.0–93.9) for overall assessment; and 73.3% (64.2–82.5), 85.0% (80.1–89.8), 81.4% (77.0–85.8), 68.0% (58.8–77.3) and 87.9% (83.4–92.5) for semi-quantitative analysis (SUVmax cut-off value 1.89 achieved by ROC analysis). Similar results were observed in the pelvis-based analysis. Conclusion: In this large single-centre series of vulvar cancer patients, [18F]FDG-PET/CT showed good values

Introduction: The study’s aim was to investigate the immunohistochemical (IHC) expression of biological markers as potential prognostic/therapeutic factors in vulvar squamous cell carcinoma (VSCC). Methodology: A series of 101 patients surgically treated at our center from 2016 to 2020 were retrospectively enrolled: 53 node-negative (Group A) and 48 node-positive (Group B). A total of 146 samples, 101 from primary tumor (T) and 45 from nodal metastases (N), were inves-tigated. The IHC panel included: p16, p53, MLH1, MSH2, MSH6, PMS2, PD-L1, CD3, HER2/neu, ER, PR, EGFR, VEGF, and CD31. The reactions were evaluated on qualitative and semi-quantitative scales. Generalized Linear Model (GLM) and cluster analysis were performed in R statistical en-vironment. A distance plot compared the IHC panel of T with the correspondent N. Results: In Group A: p16-positive expression (surrogate of HPV-dependent pathway) was significantly higher (20.8% vs. 6.2%, p = 0.04). In Group B: PD-L1 positivity and high EGFR expression were found, respectively, in 77.1% and 97.9% patients (T and/or N). Overall, p16-negative tumors showed a higher PD-L1 expression (60.9% vs. 50.0%). In both groups: tumoral immune infiltration (CD3 expression) was mainly moderate/intense (80% vs. 95%); VEGF showed strong/moderate-diffuse expression in 13.9% of T samples; CD31, related to tumoral microvessel density (MVD), showed no difference between groups; a mutated p53 and over-expressed PD-L1 showed significant association with nodal metastasis, with Odds Ratios (OR) of 4.26 (CI 95% = 1.14–15.87, p = 0.03) and 2.68 (CI 95% = 1.0–7.19, p < 0.05), respectively; since all mismatch repair proteins (MMR) showed a retained expression and ER, PR, and HER2/neu were negative, they were excluded from further analysis. The cluster analysis identified three and four sub-groups of molecular profiles, respectively, in Group A and B, with no difference in prognosis. The molecular signature of each N and corresponding T d

Objective: The aim of our systematic review was to assess the role of interventional radiotherapy (IRT, brachytherapy) in the management of primary and/or recurrent vulvar carcinoma. Evidence acquisition: A systematic research using PubMed, Scopus and Cochrane library was performed. ClinicalTrials.gov was searched for ongoing or recently completed trials, and PROSPERO was searched for ongoing or recently completed systematic reviews. Only full-text English-language articles related to IRT for treatment of primary or recurrent VC were identified and reviewed. Conference paper, survey, letter, editorial, book chapter and review were excluded. Time restriction (1990–2018) as concerns the years of the publication was considered. Evidence synthesis: Primary disease: the median 5-year LC was 43.5% (range 19–68%); the median 5-year DFS was 44.5% (range 44–81%); the median 5-year OS was 50.5% (range 27–85%). Recurrent disease: the median 5-year DFS was 64% (range 56–72%) and the median 5-year OS was 45% (range 33%-57%). Acute ≥ grade 2 toxicity was reported in three patients (1.6%). The severe late toxicity rates (grade 3–4) ranged from 0% to 14.3% (median 7.7%). Conclusion: IRT as part of primary treatment for primary and/or recurrent vulvar cancer is associated with promising clinical outcomes.

Introduction: Sentinel node biopsy (SNB) is the standard of care in women with breast cancer (BC) and clinically non suspicious axillary lymph nodes (LNs), due to its high negative predictive value (NPV) in the assessment of nodal status. SNB has significantly reduced complications related to the axillary lymph node dissection, such as lymphedema and upper limb dysfunction. Evidence acquisition: The gold standard technique for SNB is the blue dye (BD) and technetium labelled nanocolloid (Tc-99m) double technique. However, nuclear medicine is not available in all Institutions and several new tracers and devices have been proposed, such as indocyanine green (ICG) and superparamagnetic iron oxides (SPIO). All these techniques show an accuracy and detection rate not inferior to that of the standard technique, with different specific pros and cons. The choice of how to perform a SNB primarily depends on the surgeon's confidence with the procedure, the availability of nuclear medicine and the economic resources of the Institutions. In this setting, new tracers, hybrid tracers and imaging techniques are being evaluated in order to improve the detection rate of sentinel lymph nodes (SNs) and minimize the number of unnecessary axillary surgeries through an accurate preoperative assessment of nodal status and to guide new minimally invasive diagnostic procedures of SNs. In particular, the contrast-enhanced ultrasound (CEUS) is an active field of research but cannot be recommended for clinical use at this time. Evidence synthesis: The ICG fluorescence technique was superior in terms of DR, as well as having the lowest FNR. The DR descending order was SPIO, Tc, dual modality (Tc/BD), CEUS and BD. Conclusions: This paper is a narrative review of the most common SNB techniques in BC with a focus on recent innovations.

Background: Worldwide, breast cancer (BC) is the most common malignancy in the female population. In recent years, its diagnosis in young women has increased, together with a growing desire to become pregnant later in life. Although there is evidence about the detrimental effect of chemotherapy (CT) on the menses cycle, a practical tool to measure ovarian reserve is still missing. Recently, anti-Mullerian hormone (AMH) has been considered a good surrogate for ovarian reserve. The main objective of this paper is to evaluate the effect of CT on AMH value. Methods: A systematic review and meta-analysis were conducted on the PubMed and Scopus electronic databases on articles retrieved from inception until February 2021. Trials evaluating ovarian reserves before and after CT in BC were included. We excluded case reports, case-series with fewer than ten patients, reviews (narrative or systematic), communications and perspectives. Studies in languages other than English or with polycystic ovarian syndrome (PCOS) patients were also excluded. AMH reduction was the main endpoint. Egger’s and Begg’s tests were used to assess the risk of publication bias. Results: Eighteen trials were included from the 833 examined. A statistically significant decline in serum AMH concentration was found after CT, persisting even after years, with an overall reduction of -1.97 (95% CI: -3.12, -0.82). No significant differences in ovarian reserve loss were found in the BRCA1/2 mutation carriers compared to wild-type patients. Conclusions: Although this study has some limitations, including publication bias, failure to stratify the results by some important factors and low to medium quality of the studies included, this metanalysis demonstrates that the level of AMH markedly falls after CT in BC patients, corresponding to a reduction in ovarian reserve. These findings should be routinely discussed during oncofertility counseling and used to guide fertility preservation choices in young women befo

OBJECTIVE: Triple-negative breast cancers (TNBC) include a heterogeneous group of diseases, characterized by the lack of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) expression. TNBC that shows an overexpression of the androgen receptor (AR) defines the phenotype known as “luminal androgen receptor” (LAR), while the absence of the AR defines a “quadruple negative breast cancer” (QNBC). Several reports have associated AR positivity with a lower response to neoadjuvant chemotherapy (NAC), while divergent data have been reported about the impact of AR positivity on survival. The aim of this study was to retrospectively review our series of patients with TNBC tested for AR and submitted to NAC and compare pathologic complete response (pCR) rates in patients with a LAR phenotype or with QNBC. PATIENTS AND METHODS: The clinical records of all patients with TNBC tested for AR that underwent NAC at our Institution from January 1, 2015 to June 30, 2019 were reviewed. Histopathological features as well as ER, PgR, Ki67, HER2 values, clinical and pathological stage, and results of BRCA gene expression profiling were registered for all patients. RESULTS: Of the 145 TNBC patients treated by NAC, 20 (13.8%) had a LAR phenotype, while 125 (86.2%) had a QNBC. Overall, a pCR was achieved in 52 patients (35.8%). Patients with LAR phenotype had a lower rate of pCR as compared to patients with QNBC phenotype (25% vs. 37.6%). High Ki67 values (>50%) were observed less frequently in patients with a LAR phenotype (50% vs. 76.8% in QNBC). CONCLUSIONS: Our data seem to confirm that the LAR phenotype is associated to lower rates of pCR after neoadjuvant chemotherapy; routine assessment of AR expression in addition to classical biomarkers in patients with TNBC could help to better personalize treatment.

OBJECTIVE: To evaluate the feasibility and clinical applications of Fusion Virtual Navigation of 18 F-FDG PET/CT (PET/CT) and ultrasound images in assessing superficial lymph nodes in breast and gynecological cancer patients.METHODS: This is a single-center pilot study. Consecutive patients with breast or gynecological cancer with abnormal uptake of axillary or groin lymph nodes on PET/CT scan, also submitted to ultrasound assessment, were enrolled between January 2017 and May 2019. Fusion was performed acquiring PET/CT DICOM images on the ultrasound machine and synchronizing them with real time ultrasound scanning performed on the lymph node site. The abnormal lymph node was previously marked on PET/CT and retrieved during ultrasound navigation. In a first phase, we assessed the feasibility of Fusion in a series of 10 patients with suspicious lymph nodes on both PET/CT and ultrasound with full correspondence in terms of size, shape and morphology (group A). In a second phase, we included patients with un-corresponding findings between PET/CT and ultrasound: patients with a suspicious lymph node uptake on PET/CT scan and a negative ultrasound assessment (group B), and patients with suspected lymph nodes at both PET/CT and ultrasound but with no correspondence in terms of number of lymph nodes between the two techniques (group C).RESULTS: 30 patients were selected and Fusion was performed in 30 lymph node sites (22/30 inguinal, 8/30 axillary nodes). In the first phase, we evaluated 10 lymph node sites (group A) and Fusion technique was feasible in all of them. In the second phase, we selected 20 lymph node sites: 10 in group B, and 10 in group C. Fusion was successfully completed in 9/10 cases of group B and in all 10 cases of group C. In both groups Fusion was able to identify the target lymph node, guiding the examiner to perform a core needle biopsy or to inject radiotracer for selective surgical nodal excision, according to radio-guided occult lesion localization

Aim: The aims of this study were to determine the role of 18F-FDG PET/CT in vulvar cancer patients and to extract summary estimates of its diagnostic performance for preoperative lymph node staging. Patients and methods: PubMed/Medline and Embase databases were searched to identify studies evaluating 18F-FDG PET/CT in vulvar cancer patients. The assessment of methodological quality of the included articles was performed. Per-patient and per-groin pooled estimates, with 95% confidence intervals (CIs), of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic odds ratio (DOR) were calculated. Results: Ten articles were included in the systematic review, 7 among which evaluated the diagnostic performance of preoperative 18F-FDG PET/CT for lymph node staging. Qualitative per-patient analysis (72 patients from 4 studies) resulted in estimated pooled sensitivity, specificity, PPV, NPV, and DOR of 0.70 (95% CI, 0.44-0.95), 0.90 (95% CI, 0.76-1.04), 0.86 (95% CI, 0.66-1.06), 0.77 (95% CI, 0.56-0.97), and 10.49 (95% CI, 1.68-65.50), respectively. Qualitative per-groin analysis (245 groins from 5 studies) resulted in estimated pooled sensitivity, specificity, PPV, NPV, and DOR of 0.76 (95% CI, 0.57-0.94), 0.88 (95% CI, 0.82-0.94), 0.70 (95% CI, 0.55-0.85), 0.92 (95% CI, 0.86-0.97), and 19.43 (95% CI, 6.40-58.95), respectively. Conclusions: Despite limited literature data, this systematic review and meta-analysis revealed that a negative preoperative PET/CT scan may exclude groin metastases in at least early-stage vulvar cancer patients currently unfit for sentinel node biopsy and select those eligible for a less invasive surgical treatment. A positive PET/CT result should otherwise be interpreted with caution. Larger prospective studies are needed to confirm these results and to evaluate the diagnostic value of standardized semiquantitative analysis compared with the qualitative one.

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Introduction Multidisciplinary treatment strategy involving adjuvant radiotherapy for advanced vulvar cancer could be useful in offering the best personalized clinical approach. In 2013, the VULvar CANcer Multi-Disciplinary Team (Vul.Can MDT) was set up in our institution, in order to share knowledge and expertise, high-quality diagnosis, and evidence-based decision making in the context of personalized medicine. The aim of this observational study was to report on our series of vulvar cancer patients managed postoperatively with radiotherapy within the framework of a formal multidisciplinary tumor board. Methods Coupling surgical and oncological international guidelines with case-by-case discussions, a multi-specialist consensus was progressively reached and internal recommendations were developed and introduced in the daily routine. Data from vulvar cancer patients who underwent primary surgery and adjuvant radiotherapy throughout a 5-year period were retrospectively collected. Actuarial local control was the primary endpoint, while secondary end-points were acute and late toxicities, disease-free survival, and overall survival. Toxicity was evaluated according to the Common Toxicity Criteria Adverse Event v 4.0 scale. Results The analysis included 35 patients with squamous vulvar cancer treated with adjuvant radiotherapy±chemotherapy, from April 2013 to September 2017. Median age was 70 years (range 18-87), all patients underwent surgery followed by concomitant chemoradiation (45.7%) or radiotherapy alone (54.3%). The median prophylactic dose on lymphatic drainage was 45 Gy, while positive nodes and perineal area received 51.2 Gy and 52.6 Gy, respectively. Chemotherapy involved the cisplatin-based regimen (45.7%)±5-fluorouracil (37.1%). Median follow-up was 32 months (range 6-72): the 24-months local control, disease-free survival, and actuarial overall survival rates were 88.6%, 82.0%, and 91.0%, respectively. Low rates of severe acute (12%) and late (3%) toxici

Introduction: Since the community spread of Coronavirus disease 2019 (COVID-19), the practice of oncologic care at our comprehensive cancer center has changed. Postponing cancer treatment without consideration of its implications could cost more lives than can be saved. In this special situation, we must continue to provide our cancer patients with the highest quality of medical services assuring the safety. This article provides general guidance on supporting curative treatment strategies in vulvar cancer patients. Methods: At our institution, a vulvar cancer multidisciplinary team (Vul.Can MDT) of specialists is responsible for personalized treatment of this disease. The phase 2 period necessarily requires specific procedures for both outpatient and inpatient pathways and to provide strategies concerning the management of vulvar cancer patients even in case of an eventually concomitant SARS-CoV-2 infection. In brief, an accurate remote and in person triage must be provided routinely and patients submitted to specific diagnostic tests prior to every major treatment or procedure (surgery, RT, and CT) or in case of suspicion for COVID-19 syndrome. The decisional workflow for these women often old and frail, have been rapidly adjusted by our Vul.Can MDT to mitigate the potential risks of COVID-19. Results: The team produced two types of recommendations concerning: (1) safety regulations of care pathways, patients and health care providers, (2) personalized treatment strategies. We present a protocol that can be applied in clinical practice: the flowcharts provided, include the modulation of treatment intensity designed for surgical procedures and radiation, stratified for FIGO stage of disease and intention. Conclusion: We suggest that our proposals are applicable in this setting of patients, considering anyway current international recommendations and guidelines.

Background: Additional prognostic factors and personalized therapeutic alternatives for vulvar squamous cell carcinoma (VSCC), especially for advanced stages with poor prognosis, are urgently needed. Objectives: To review and assess literature regarding underlying molecular mechanisms of VSCC target therapeutic and prognostic approaches. Methods: We performed a narrative literature review from the inception of the database up to January 2020 limited to English language, organizing knowledge in five main fields: extracellular and intracellular cell cycle deregulation, tumor immune microenvironment, tumor angiogenesis and hormones. Results: EGFR immunohistochemical overexpression/gene amplification, representing early events in VSCC carcinogenesis, have been correlated with a worse prognosis and led to inclusion of erlotinib in cancer guidelines. p16 expression and HPV positivity are linked to a better prognosis, while p53 overexpression is linked to a worse prognosis; thus, biomarkers could help tailoring conventional treatment and follow-up. The implications of PD-L1 positivity in reference to HPV status and prognosis are still not clear, even though pembrolizumab is part of available systemic therapies. The role of tumor angiogenesis emerges through data on microvessel density, immunohistochemical VEGF staining and evaluation of serum VEGF concentrations. Few data exist on hormonal receptor expression, even though hormonal therapy showed great manageability. Conclusions: We suggest adding p16, p53 and HPV status to routine hystopathological examination of vulvar biopsies or surgical specimens. Predictive biomarkers for anti-EGFR and anti-PD-1/PD-L1 drugs are needed. Enough preclinical data supporting anti-angiogenic target therapies in clinical trials are existing. Hormonal receptor expression deserves further investigation.

Objective Since vulvar cancer is such a rare disease, the international experience with electrochemotherapy has been derived from only a few centers. The aim of this study was to evaluate clinical outcome and side effects profile with the use of electrochemotherapy in patients with primary or recurrent vulvar cancer. Methods Data were retrospectively collected from November 2017 to November 2019 in two major Italian oncologic institutes: Regina Elena Institute and Fondazione Policlinico Universitario Agostino Gemelli IRCCS. Electrochemotherapy was offered in a palliative setting to patients with a primary or recurrent vulvar cancer who were not candidates for surgery or any other treatment, because of poor performance status or previous delivered treatments. All patients underwent general anesthesia. Electrical pulses were delivered using a pulse generator. Intravenous bleomycin was administered in conjunction with electrochemotherapy. Follow-up examinations were performed at 1, 3, and 6 months. Primary endpoint was to assess the response rate of electrochemotherapy as palliative treatment in patients with vulvar cancer. Results A total of 15 patients were included in the study. Fourteen patients (93.3%) had a squamous cell carcinoma and one patient had vulvar carcinosarcoma. Ten patients (66.7 %) had a single lesion and 5 patients (33.3%) had multiple lesions. Median number of electrical pulses was 22 (range 3-42) and median operative time was 13 (range 7-20) min. No intra-procedure complications occurred. One patient had pneumonia during their post-operative stay. Overall response rate after 1 month was 80%. At the 3-month follow-up, 3 patients (20%) had disease progression, 3 patients (20%) had died from ongoing disease, 1 patient (6.7%) died for other reasons, whereas the other patients maintained their 1-month clinical response. A total of 8/13 patients (61.5%) were alive at 6-month follow-up, whereas 6/12 patients (50%) were alive at 1-year follow-up. Conclusi

Objective: To assess the accuracy of preoperative ultrasound examination for predicting lymph-node (LN) status in patients with vulvar cancer. Methods: This was a single-institution retrospective observational study of all women with a histological diagnosis of vulvar cancer triaged to inguinal surgery within 30 days following ultrasound evaluation between December 2010 and January 2016. For each groin examined, 15 morphological and dimensional sonographic parameters associated with suspicion for LN involvement were examined. A morphometric ultrasound pattern (MUP) was expressed for each groin, classifying the inguinal LN status into five groups (normal; reactive-but-negative; minimally suspicious/probably negative; moderately suspicious; and highly suspicious/positive) according to subjective judgment, followed by stratification as positive or negative for metastasis according to morphometric binomial assessment (MBA). In cases of positive MBA, fine-needle aspiration cytology was performed. Combining the information obtained from MUP and cytologic results, a binomial final overall assessment (FOA) was assigned for each groin. The final histology was considered as the reference standard. Comparison was performed between patients with negative and those with positive LNs on histology, and receiver-operating-characteristics curves were generated for statistically significant variables on univariate analysis, to evaluate their diagnostic ability to predict negative LN status. Results: Of 144 patients included in the analysis, 87 had negative inguinal LNs and 57 had positive LNs on histology. A total of 256 groins were analyzed, of which 171 were negative and 85 showed at least one metastatic LN on histology. The following parameters showed the greatest accuracy, with the best balance between specificity and sensitivity, in predicting negative LN status: cortical (C) thickness of the dominant LN (cut-off, 2.5 mm; sensitivity, 90.0%; specificity, 77.9%); short-axis (S) l

Immunotherapy can be used for cutaneous, mucosal, uveal and conjunctival melanoma. Nevertheless, we cannot expect the same benefit from checkpoint inhibitors for all the types of melanoma. The different biological features can explain the variable efficacy. The main results obtained with immune checkpoint inhibitors in the various types of melanoma were reviewed.

Pathogenic mutations in two autosomal dominant genes, BRCA1 and BRCA2, with high penetrance are supposed to be the cause for an approximated 5-7% risk of all breast cancer (BC) and ovarian cancer (OC). Compared to sporadic BC, BRCA mutated (BRCAmut) BC differs for lifetime risk of onset and sensitivity to systemic therapies. A hereditary BC syndrome should be taken into account when there are numerous relatives with BC early-onset (typically before menopause). Moreover, BRCAmut carriers showed a lifetime possibility of manifesting OC. When a BC diagnosis is made in young patients or in suspicious personal relatives' anamnesis, be aware of being carriers of a BRCA mutation may influence the decision making-process about surgical procedure and prevention strategies. In this review, we examined surgical treatment choice for BRCAmut BC, risk of ipsilateral breast recurrence (IBR) and contralateral breast cancer (CBC). We examined the role of breast-conserving therapy (BCT), risk-reducing mastectomy (RRM) and preventive risk-reducing salpingo-oophorectomy (RRSO) with a special consideration about advantage in terms of mortality reduction for both conservative and prophylactic measures. We also reviewed the sensitivity of mutated BC to platinum-based antineoplastic drugs and poly (ADP-ribose) polymerase inhibitors (PARPi) by emphasizing the results of clinical trials recently published.

This study aimed to assess the value of dual-timepoint 18F-FDG PET/CT in the prediction of lymph node (LN) status in patients with invasive vulvar cancer (VC) scheduled for inguinofemoral LN dissection. Methods: From April 2013 to July 2015, all consecutive patients with VC scheduled for inguinofemoral LN dissection were prospectively enrolled. All patients underwent a preoperative whole-body 18F-FDG PET/CT scan at 1 h (standard examination) and an additional scan from T11 to the groins at 3 h (delayed examination) after 18F-FDG injection. On both scans, each groin was visually scored 0 or 1 concerning 18F-FDG LN uptake relative to background. Semiquantitative analysis included SUVmax and the corresponding retention index of SUVmax, measured on both scans. The optimal cutoff value of these parameters was defined using a receiveroperating- characteristic analysis. Histopathology was the standard of reference. Results: Thirty-three patients were included, with a total of 57 groins dissected and histologically evaluated. At histopathology, 21 of 57 (37%) groins contained metastatic LNs. Concerning visual score, sensitivity, specificity, negative predictive value, positive predictive value, and accuracy were 95.2%, 75%, 96.4%, 69%, and 82.5% on standard scanning and 95.2%, 77.8%, 96.6%, 71.4%, and 84.2% on delayed scanning, respectively. At receiver-operating-characteristic analysis, sensitivity and specificity were 95.2% and 77.8% on standard and delayed 18F-FDG PET/CT for an SUVmax cutoff of greater than 1.32 and 1.88, respectively, and 95.2% and 80% for a retention index of SUVmax cutoff of greater than 0. Conclusion: Standard 18F-FDG PET/CT is an effective preoperative imaging method for the prediction of LN status in VC, allowing the prediction of pathologically negative groins and thus the selection of patients suitable for minimally invasive surgery. Delayed 18F-FDG PET/CT did not improve the specificity and the positive predictive value in our series. Larger stu

Objective The study aims were: 1) to verify the role of sentinel node biopsy (SNB) in a subset of patients with clinical N0 (cN0) invasive vulvar cancer (VC) who were still candidates for radical inguinal surgery according to the current guidelines; 2) to investigate whether a preoperative18F-FDG PET/CT (PET/CT) evaluation could improve the selection of node negative patients. Methods From July 2013 to July 2016, all patients with VC admitted to our Division were evaluated by standard imaging and clinical exam. Among the patients assessed as cN0 we enrolled those unsuitable for SNB, due to: T > 4 cm, multifocal tumors, complete tumor diagnostic excision, contralateral nodal involvement and local recurrence. A preoperative PET/CT was performed. For each patient surgery included SNB, performed using a combined technique (radiotracer plus blue dye), followed by standard inguino-femoral lymphadenectomy. The reference standard was histopathology. Results Forty-seven patients entered the study for a total of 73 groins. Histopathology revealed 12 metastatic SNs in 9 groins. No false negative SNs were found (NPV 100%). PET/CT showed a negative predictive value of 93%. Conclusions Our data suggest that SNB is accurate and safe even in cN0 patients currently excluded from this procedure, providing that a careful preoperative selection is performed. PET/CT allows a reliable assessment of LN status and may be an effective support for the selection of patients who are safe candidates for SNB.